ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.578C>T (p.Ala193Val)

gnomAD frequency: 0.00002  dbSNP: rs750266156
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189687 SCV000243333 uncertain significance not provided 2015-01-09 criteria provided, single submitter clinical testing p.Ala193Val (GCG>GTG): c.578 C>T in exon 2 of the TBC1D24 gene (NM_001199107.1). A variant of unknown significance has been identified in the TBC1D24 gene. The A193V variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A193V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals but is not conserved in more distantly related species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSYV2-1 panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV002514070 SCV003461188 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2022-07-14 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 207500). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. This variant is present in population databases (rs750266156, gnomAD 0.006%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 193 of the TBC1D24 protein (p.Ala193Val).

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